In this game, finding Lucrecia is optional, but provides an important history for both Vincent Valentine and Sephiroth. She is indicated to be Sephiroth's mother and suggests that she knew of the horrific events that would come to pass. The guilt over her own actions and those of her son drove her to trap herself in the mako crystals for eternity. Vincent's own guilt over doing nothing to help Lucrecia plague him throughout the journey to stop Sephiroth. When she asks if her son is dead, Vincent falsely tells her that he is.

Lucrecia's life is explored through flashbacks in this game. Initially, Lucrecia worked as an assistant to Vincent's father, Grimoire Valentine. During this time, they found evidence of the WEAPONs and of Chaos. Lucrecia eagerly studied Chaos in the lab, but its unstable nature eventually caused Grimoire's death.

When Lucrecia became a scientist under Hojo, Vincent Valentine, then a Turk, was assigned to be her bodyguard. It is insinuated that the two were romantically involved, but when Vincent found out that Lucrecia worked with his father, she left him due to her strong feelings of guilt over Grimoire's death. She ran instead into Hojo's arms and subsequently becomes pregnant.

Lucrecia encased in mako crystal.

Lucrecia agreed to use her unborn child in the Jenova Project, being injected with Jenova cells. Lucrecia then began having visions of her son falling into madness and causing great destruction. When Vincent confronted Hojo about Lucrecia, Hojo shot him and used his body in his experiments. Hojo would eventually cast off Vincent as a failure, and Lucrecia used her Chaos theory to keep Vincent alive. Upon seeing Vincent's transformation into the volatile Chaos, Lucrecia infused Vincent with the Protomateria in order to help him control the demon.

Shortly after, Hojo taunted Lucrecia over her use of her former love as an experiment, and when she demanded to see her son, Hojo denied her. Completely distraught, Lucrecia left behind her notes on Chaos and Omega, and turned to suicide. Unable to die due to Jenova's cells, Lucrecia instead encased herself in mako crystals in a hidden cave.